1. Field of the Invention
The present invention relates to novel processes for producing phosphinopyrrolidine compounds which are chiral ligands for catalysts effective in asymmetric synthesis and to novel intermediate compounds which are products in the processes. Said processes enable us to simplify production steps including complicated multi-stages and further to make not only a manufacturing apparatus but also facilities for processes simple.
2. Description of the Related Art
Pantolactone is extensively utilized as a starting material for synthesizing pharmaceuticals, etc. Particularly, D-pantolactone (R-(-)-pantolactone) is well known as an intermediate in the preparation of D-pantothenic acid and pantethine which are useful as vitamins of medical or physiological importance. Since pantolactone has an asymmetric center in its molecule, chemically synthesized pantolactone products usually require optical resolution. In other words, D-pantolactone is prepared via the optical resolution of chemically synthesized D,L-pantolactone. Such a synthesis including the optical resolution is not only complicated and burdensome but also disadvantageous, such as costly. Specifically, the optical resolution has disadvantages in that it requires special agents, etc. and skills of operating it. That is, the process utilizing the optical resolution requires the use of expensive optical resolving agents such as quinine or brucine and further has defects in the recovery of D-pantolactone (it is not easy to recover D-pantolactone), etc. For means for solving these problems, a proposal of synthesizing optically active pantolactone by production processes utilizing an asymmetrically synthesizing reaction has been provided (U.S. Pat. No. 4,879,389).
For the process disclosed in U.S. Pat. No. 4,879,389, it has been reported that optically active pantolactone is prepared enantioselectively in quite excellent yields from an industrial standpoint by asymmetric hydrogenation using the phosphinopyrrolidine compounds; however, the synthesis of the phosphinopyrrolidine compounds, important reagents for the process, requires multi-processes including totally 14 steps, thereby incurring a drawback such as a demand for totally great expenditures. In the prior art process of synthesizing the phosphinopyrrolidine compounds, it is also essential to take a step of converting diphenylphosphino groups into dicyclohexylphosphino groups wherein benzene nuclei in the 4-diphenylphosphino are hydrogenated. The prior art hydrogenation conversion requires reactions at highly elevated temperatures and pressures (e.g., 150.degree. C. and 150 atm), whereby there has been a drawback such as a demand for special facilities. Especially in industrial production, it is not easy to fit manufacturing facilities thereto. Further, such fitting facilities cost very much and are still accompanied with risks upon the manufacturing operation.
The phosphinopyrrolidine compounds are excellent reagents useful in catalytic asymmetric syntheses for not only pantolactone but also a wide variety of optically active compounds. Therefore, if it is feasible to synthesize the phosphinopyrrolidine compounds readily, efficiently, or unexpensively, it may enable us to apply such reagents to a diversity of asymmetric syntheses. Thus, to develop a production technique suited for these purposes is strongly demanded.